Biology | Epigenetics, Chromosome&Disease
L411 | 31105 | Pikaard, C


L411   Epigenetics, chromosomes and disease

Epigenetic phenomena are the X-files of genetics – cases in which
genes do not obey Mendel’s rules of inheritance but display
variable, sometimes unpredictable expression patterns. Some
epigenetic phenomena occur as part of normal development but others
are implicated in disease states, including cancer, fragile X
syndrome, Prader-Willi syndrome, Angelman syndrome, Rett Syndrome,
mad cow disease, and Alzheimer’s syndrome.  Most epigenetic
phenomena are chromosomal in nature and involve gene silencing
caused by chemical modifications of the DNA or the chromatin
proteins that organize the DNA. Some of these modifications can
influence gene-expression states for three or more generations –
from grandparents to grandchildren. Other epigenetic phenomena
involve shape-shifting proteins that can convert to a so-called
prion state and cause identical proteins in the cell to change shape
as well.

In this course, we will conduct a case-study examination of some of
the most fascinating epigenetic phenomena and explore their
mechanistic basis at a molecular level. Among the topics we will
explore are: DNA, chromatin and chromosome structures; DNA
methylation and histone post-translational modifications; position-
effect variegation in flies and yeast; X-chromosome inactivation in
female mammals (the basis for the calico phenotype in female cats;
Barr bodies); sex-chromosome dosage compensation in flies, worms,
and birds; gametic imprinting causing uniparental inheritance;
paramutation, the heritable change in allele expression state upon
exposure to a related allele; nucleolar dominance – the uniparental
silencing of ribosomal RNA genes in genetic hybrids; vernalization
(memory of winter) and flowering in plants; transgenerational
inheritance of gene-expression changes caused by the effect of diet
(folate) on DNA methylation; homology-dependent gene silencing in
plants, worms, vertebrates, etc.;  silencing of transposons,
viruses, and other forms of genome defense; roles of noncoding RNAs
(siRNAs, miRNAs, piRNAs) in gene silencing; molecular mechanisms for
epigenetic inheritance through meiosis and/or mitosis;
heterochromatin in gene silencing and chromosome segregation; prions
and prion-associated diseases (e.g. Mad cow disease, scrapie, kuru,
Creutzfeldt-Jakob syndrome, Alzheimer’s disease); and diseases and
disorders caused by aberrant chromatin modifications , including
cancer, Prader-Willi syndrome, Angelman syndrome, Rett Syndrome, ICF
syndrome, and Fragile X syndrome.